Humans are a natural reservoir for Gram-positive Staphylococcus aureus. For example, S. aureus can colonize the skin, nares and throat, either permanently or transiently, without causing disease. S. aureus infections range from mild skin infections to endocarditis, osteomyelitis, bacteremia and sepsis. S. aureus also causes a majority of nosocomial infections, and its prevalence in community-onset infections is increasing. Moreover, in 2005, methicillin-resistant S. aureus (MRSA) infections were estimated at 31.8 per 100,000 individuals, including 16,650 deaths in the United States in 2005 (Klevens et al. (2007) J. Am. Med. Assoc. 298:1763-1771). Disease subsequently occurs when individuals become immunocompromised due to breaches in immune barriers, such as during surgery, placement of indwelling catheters or other devices, trauma or wounds.
S. aureus produces a large number of extra- and intra-cellular antigens, including numerous toxins and enzymes. Of particular interest herein are capsular polysaccharide serotypes of S. aureus (see, Karakawa & Vann, “Capsular polysaccharides of Staphylococcus aureus,” In: Weinstein & Fields, eds. Seminars in Infectious Disease. IV. Bacterial Vaccines. (New York, N.Y.; Thieme Stratton; 1982. pp. 285-293), especially serotype 5 and 8 capsular polysaccharides. Epidemiological studies on a large number of strains of S. aureus isolated from individuals showed that 70% to 80% were either serotype 5 or 8 capsular polysaccharide (Arbeit et al. (1984) Diagn. Microbial. Infect. Dis. 2:85-91). Unfortunately, the capsular polysaccharides are poor immunogens by themselves.
Staphylococcal infections and diseases dramatically increased in the last twenty years, as has use of intravascular devices and invasive procedures. The rise in disease incidence is more troubling because of a parallel rise of antibiotic resistance; therefore, there is an urgent need for immunogenic compositions to prevent Staphylococcal infections and diseases.